Inflammatory reaction is accompanied by infiltration of leukocytes, typically neutrophils and lymphocytes, into inflammatory sites.
Infiltration of leukocytes is defined as migration of leukocytes such as neutrophils and lymphocytes out of vessels and into the surrounding tissues as a consequence of initiation and activation by cytokines, chemokines, lipids and complement to interact called “rolling” or “tethering” with vascular endothelial cells activated by cytokines such as IL-1 or TNFα, followed by adhesion to the vascular endothelial cells.
A relationship between leukocyte adhesion or infiltration and various inflammatory diseases and autoimmune diseases was reported (See, for example, the documents cited in (1)-(7) below). In particular, the possibility that compounds having cell adhesion inhibitory action or cell infiltration inhibitory action may serve as therapeutic or prophylactic agents for such diseases has been raised.    (1) Therapeutic or prophylactic agents for inflammatory bowel diseases (ulcerative colitis, Crohn's disease and the like) (see (a) Podolsky et al., “Inflammatory bowel disease”, N. Engl. J. Med., 347(6): 417-429, 2002; (b) Ghosh et al., “Natalizumab for active Crohn's disease”, N Engl J Med, 348(1): 24-32, 2003; and (c) Shimoyama et al., “Granulocyte and monocyte apheresis with the G-1 column in the treatment of patients with active ulcerative colitis”, Japanese Journal of Apheresis, 18(1): 117-131, 1999)    (2) Therapeutic or prophylactic agents for irritable bowel syndrome (see Barbara et al., “A role for inflammation in irritable bowel syndrome?”, Gut, 51(Suppl. 1): i41-i44, 2002)    (3) Therapeutic or prophylactic agents for rheumatoid arthritis (see Sweeney et al., “Rheumatoid arthritis: regulation of synovial inflammation”, The International Journal of Biochemistry & Cell Biology, 36: 372-378, 2004)    (4) Therapeutic or prophylactic agents for psoriasis (see Lebwohl M., “Psoriasis”, Lancet, 361: 1197-1204, 2003)    (5) Therapeutic or prophylactic agents for multiple sclerosis (see Polman et al., “New and emerging treatment options for multiple sclerosis”, The Lancet neurology, 2: 563-566, 2003)    (6) Therapeutic or prophylactic agents for asthma (see Larché et al., “The role of T lymphocutes in the pathogenesis of asthma”, J. Allergy Clin. Immunol., 111(3): 450-463, 2003)    (7) Therapeutic or prophylactic agents for atopic dermatitis (see Schön, et al., “The molecular basis of lymphocyte recruitment to the skin: Clues for pathogenesis and selective therapies of inflammatory disorders”, The Journal of Investigative Dermatology, 121(5): 951-962, 2003)
Thus, substances which inhibit cell adhesion or cell infiltration are expected to be useful as therapeutic or prophylactic agents for inflammatory diseases and autoimmune diseases and as therapeutic or prophylactic agents for various diseases associated with adhesion and infiltration of leukocytes, such as inflammatory bowel disease (particularly ulcerative colitis or Crohn's disease), irritable bowel syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, asthma and atopic dermatitis.
Compounds are also known which have anti-inflammatory action based on inhibition of adhesion of leukocyte and vascular endothelial cell, or anti-inflammatory action based on inhibition of leukocyte infiltration (these will hereinafter be referred to as cell adhesion inhibitors and cell infiltration inhibitors, respectively), such as the following compound:
(see WO 2002/018320).
However, in one aspect, the compounds represented by general formula (1) according to the present invention are characterized by including a partial chemical structure having piperazine or piperidine at the ortho position of a benzene ring bonded to an aliphatic carbocyclic group such as cyclohexyl, therefore differ in their structures from the aforementioned cell adhesion inhibitors or cell infiltration inhibitors.
Patent publication WO 2002/059108 discloses the following compound:

However, WO 2002/059108 discloses only its use as an anti-obesity agent and diabetes treatment based on the melanocortin receptor agonistic activity of the compound, while it neither discloses nor suggests its use as an anti-inflammatory agent based on inhibitory action of leukocyte adhesion or infiltration.
Other than the above compound, the compound represented by the following formula:
is known (see Cowart et al., “Discovery of 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole (ABT-724), a Dopaminergic agent with novel mode of action for the potential treatment of erectile dysfunction”, J. Med. Chem., 47: 3853-3864, 2004, compound number 45).